Abstract

Insufficient sleep is associated with numerous negative effects as cognitive impairment, mental disorders and cardiovascular diseases. To fully understand how sleep deprivation (SD) can lead to these impairments and conditions, it is essential to know the underlying mechanisms. Despite the consensus about the importance of sleep as a restorative mechanism, the processes behind this are still to be fully described. Here, I hypothesize that reduced clearance of waste products in the brain and epigenetic changes to DNA form the basis of the long-lasting consequences of sleep deprivation. In peripheral tissue, lymph vessels are used to return excess metabolites and proteins into the blood stream. The brain does not have lymph vessels and returns its metabolites to the blood circulation via the glymphatic system. Astrocytic aquaporin-4 water channels (AQP4) conduct water through the cell membrane, stimulating convective flow. The increased flow increases
cerebrospinal fluid (CSF) and interstitial fluid (ISF) interactions. This process is extensively reduced (>60%) during wakefulness thus leading to increased metabolite and waste product levels in the brain. These waste products can cause long-lasting DNA damage and are shown to be involved with neurodegenerative diseases such as Alzheimer. Additionally, sleep deprivation has shown to alter DNA methylation patterns of the genome. DNA methylation is an epigenetic process in which a methyl (CH3) group is added to the DNA, altering the function of genes. This is a stable modification that can suppress gene expression over a lifespan. Previous studies have showed that DNA methylation is a way to adapt to (stressful) environmental conditions by altering gene expression.
These adaptations may also occur in situations of prolonged sleep deprivation, though at the cost of increased chance for diseases and cognitive impairments. Hypothesizing the mechanisms behind
these negative consequences can lead to a better understanding of the underlying processes involved in sleep deprivation.